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Levodopa effects on [ (11)C]raclopride binding in the resting human brain.

Black KJ, Piccirillo ML, Koller JM, Hseih T, Wang L, Mintun MA - F1000Res (2015)

Bottom Line: Levodopa did not significantly reduce striatal RAC* binding and striatal binding did not differ significantly between TS and control groups.However, levodopa's effect on DA release differed significantly in a right midbrain region (p=0.002, corrected), where levodopa displaced RAC* by 59% in control subjects but increased BP ND by 74% in TS subjects.We hypothesize that mesostriatal DA neurons fire relatively little while subjects rest, possibly explaining the non-significant effect of levodopa on striatal RAC* binding.

View Article: PubMed Central - PubMed

Affiliation: Departments of Psychiatry, Neurology, Radiology, and Anatomy & Neurobiology, Washington University School of Medicine, St. Louis, MO, 63110, USA.

ABSTRACT

Rationale: Synaptic dopamine (DA) release induced by amphetamine or other experimental manipulations can displace [ (11)C]raclopride (RAC*) from dopamine D2-like receptors. We hypothesized that exogenous levodopa might increase dopamine release at striatal synapses under some conditions but not others, allowing a more naturalistic assessment of presynaptic dopaminergic function. Presynaptic dopaminergic abnormalities have been reported in Tourette syndrome (TS).

Objective: Test whether levodopa induces measurable synaptic DA release in healthy people at rest, and gather pilot data in TS.

Methods: This double-blind crossover study used RAC* and positron emission tomography (PET) to measure synaptic dopamine release 4 times in each of 10 carbidopa-pretreated, neuroleptic-naïve adults: before and during an infusion of levodopa on one day and placebo on another (in random order). Five subjects had TS and 5 were matched controls. RAC* binding potential (BP ND) was quantified in predefined anatomical volumes of interest (VOIs). A separate analysis compared BP ND voxel by voxel over the entire brain.

Results: DA release declined between the first and second scan of each day (p=0.012), including on the placebo day. Levodopa did not significantly reduce striatal RAC* binding and striatal binding did not differ significantly between TS and control groups. However, levodopa's effect on DA release differed significantly in a right midbrain region (p=0.002, corrected), where levodopa displaced RAC* by 59% in control subjects but increased BP ND by 74% in TS subjects.

Discussion: Decreased DA release on the second scan of the day is consistent with the few previous studies with a similar design, and may indicate habituation to study procedures. We hypothesize that mesostriatal DA neurons fire relatively little while subjects rest, possibly explaining the non-significant effect of levodopa on striatal RAC* binding. The modest sample size argues for caution in interpreting the group difference in midbrain DA release with levodopa.

No MeSH data available.


Related in: MedlinePlus

Stability of baseline binding between scan days in thea priori VOIs.BPNDs from the first scan of each day are plotted for all 10 subjects, with the BPND from the pre-placebo scan on the horizontal axis and from the pre-levodopa scan on the vertical axis. For the paired VOIs the mean of the left and right BPND is used. The diagonal line is the line of identity. The inset shows an enlarged view of the data from the frontal lobe and thalamus VOIs.
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f4: Stability of baseline binding between scan days in thea priori VOIs.BPNDs from the first scan of each day are plotted for all 10 subjects, with the BPND from the pre-placebo scan on the horizontal axis and from the pre-levodopa scan on the vertical axis. For the paired VOIs the mean of the left and right BPND is used. The diagonal line is the line of identity. The inset shows an enlarged view of the data from the frontal lobe and thalamus VOIs.

Mentions: Thea priori VOIs showed higher and more reliable binding in striatum and pallidum, as expected. Nevertheless, the thalamus, GP and frontal cortex VOIs also produced good counting statistics (Figure 3). For every one of the VOIs the baseline BPND estimates were positive in all 120 scans, and were very similar between the two scan days (Table 4,Figure 4).


Levodopa effects on [ (11)C]raclopride binding in the resting human brain.

Black KJ, Piccirillo ML, Koller JM, Hseih T, Wang L, Mintun MA - F1000Res (2015)

Stability of baseline binding between scan days in thea priori VOIs.BPNDs from the first scan of each day are plotted for all 10 subjects, with the BPND from the pre-placebo scan on the horizontal axis and from the pre-levodopa scan on the vertical axis. For the paired VOIs the mean of the left and right BPND is used. The diagonal line is the line of identity. The inset shows an enlarged view of the data from the frontal lobe and thalamus VOIs.
© Copyright Policy - open-access
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4490799&req=5

f4: Stability of baseline binding between scan days in thea priori VOIs.BPNDs from the first scan of each day are plotted for all 10 subjects, with the BPND from the pre-placebo scan on the horizontal axis and from the pre-levodopa scan on the vertical axis. For the paired VOIs the mean of the left and right BPND is used. The diagonal line is the line of identity. The inset shows an enlarged view of the data from the frontal lobe and thalamus VOIs.
Mentions: Thea priori VOIs showed higher and more reliable binding in striatum and pallidum, as expected. Nevertheless, the thalamus, GP and frontal cortex VOIs also produced good counting statistics (Figure 3). For every one of the VOIs the baseline BPND estimates were positive in all 120 scans, and were very similar between the two scan days (Table 4,Figure 4).

Bottom Line: Levodopa did not significantly reduce striatal RAC* binding and striatal binding did not differ significantly between TS and control groups.However, levodopa's effect on DA release differed significantly in a right midbrain region (p=0.002, corrected), where levodopa displaced RAC* by 59% in control subjects but increased BP ND by 74% in TS subjects.We hypothesize that mesostriatal DA neurons fire relatively little while subjects rest, possibly explaining the non-significant effect of levodopa on striatal RAC* binding.

View Article: PubMed Central - PubMed

Affiliation: Departments of Psychiatry, Neurology, Radiology, and Anatomy & Neurobiology, Washington University School of Medicine, St. Louis, MO, 63110, USA.

ABSTRACT

Rationale: Synaptic dopamine (DA) release induced by amphetamine or other experimental manipulations can displace [ (11)C]raclopride (RAC*) from dopamine D2-like receptors. We hypothesized that exogenous levodopa might increase dopamine release at striatal synapses under some conditions but not others, allowing a more naturalistic assessment of presynaptic dopaminergic function. Presynaptic dopaminergic abnormalities have been reported in Tourette syndrome (TS).

Objective: Test whether levodopa induces measurable synaptic DA release in healthy people at rest, and gather pilot data in TS.

Methods: This double-blind crossover study used RAC* and positron emission tomography (PET) to measure synaptic dopamine release 4 times in each of 10 carbidopa-pretreated, neuroleptic-naïve adults: before and during an infusion of levodopa on one day and placebo on another (in random order). Five subjects had TS and 5 were matched controls. RAC* binding potential (BP ND) was quantified in predefined anatomical volumes of interest (VOIs). A separate analysis compared BP ND voxel by voxel over the entire brain.

Results: DA release declined between the first and second scan of each day (p=0.012), including on the placebo day. Levodopa did not significantly reduce striatal RAC* binding and striatal binding did not differ significantly between TS and control groups. However, levodopa's effect on DA release differed significantly in a right midbrain region (p=0.002, corrected), where levodopa displaced RAC* by 59% in control subjects but increased BP ND by 74% in TS subjects.

Discussion: Decreased DA release on the second scan of the day is consistent with the few previous studies with a similar design, and may indicate habituation to study procedures. We hypothesize that mesostriatal DA neurons fire relatively little while subjects rest, possibly explaining the non-significant effect of levodopa on striatal RAC* binding. The modest sample size argues for caution in interpreting the group difference in midbrain DA release with levodopa.

No MeSH data available.


Related in: MedlinePlus